Efficacy, safety and tolerability of two Fixed-Dose Combinations of Aclidinium bromide with two doses of Formoterol fumarate compared with Aclidinium bromide, Formoterol fumarate and placebo all administered twice daily in stable, moderate to severe Chronic Obstructive Pulmonary Disease patients.

• Conditions: Moderate to severe chronic obstructive pulmonary disease (COPD); MedDRA version: 12.0Level: LLTClassification code 10009033Term: Chronic obstructive pulmonary disease

• Registration Number: EUCTR2009-015901-38-DE
• Lead Sponsor: ALMIRALL, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-11
• Last Update Posted: 17 December 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Adult male or non-pregnant, non-lactating female aged between 40 and 80 years old, both inclusive. Female of childbearing potential must have a negative pregnancy test at Screening and be using a medically acceptable method of contraception (either double-barrier contraception or a barrier method plus a spermicidal or hormonal agent).
(A female is considered to be of childbearing potential unless she is at least 1 year postmenopausal or surgically sterile (defined as having a hysterectomy or tubal ligation)).
2. Patient with a clinical diagnosis of stable moderate to severe COPD (stages II and III) according to the GOLD classification (http://www.goldcopd.com).
3. Current, or ex-cigarette smoker with a smoking history of at least 10 pack-years.
Pack-years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person has smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years would have a 20 pack-year smoking history (40 cigarettes per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history). (Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well).
4. Patient whose FEV1 at the Screening Visit measured between 10-15 minutes post inhalation of 400 µg of salbutamol is 30% = FEV1 <80% of the predicted normal value (i.e., 100 x Postsalbutamol FEV1/ Predicted FEV1 must be < 80% and = 30%).
(Predicted normal values to be used for calculation purposes are to be based on European Community for Steel and Coal predicted values (Quanjer et al. 1993)19).
5. Patient whose FEV1/FVC at the Screening Visit measured between 10-15 minutes post inhalation of 400 µg of salbutamol is < 70% (i.e., 100 x Post-salbutamol FEV1 /FVC < 70%).
6. Patient who is eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained.

In addition, before randomisation:
7. Patient whose COPD symptoms and FEV1 values at the time of randomisation are stable
compared to the Screening Visit, according to the investigator’s medical judgment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. History or current diagnosis of asthma or exercise-induced bronchospasm.
2. Clinically significant respiratory conditions at the time of Inform Consent signature defined as:
• Use of long-term oxygen therapy > 15h/day,
• Known active tuberculosis or history of lung cancer,
• History of interstitial lung or pulmonary thromboembolic disease,
• Pulmonary resection or surgery during the past 12 months,
• History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener’s syndrome, etc),
• Patients who in the investigator’s opinion may need to stop or start pulmonary rehabilitation or undergo a thoracotomy during the trial,
3. Hospitalisation due to COPD exacerbation within the previous 3 months.
4. Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract) within the previous 6 weeks.
5. Patient on pulmonary rehabilitation program for less the 6 weeks.
6. Patient who has a resting systolic blood pressure = 200 mmHg, a resting diastolic blood pressure =120 mmHg or a resting heart rate = 105 bpm at screening visit.
7. Clinically significant cardiovascular conditions defined as:
• Myocardial infarction within the previous 6 months,
• Unstable arrhythmia which has required changes in the pharmacological therapy or other intervention within the previous 12 months, or newly diagnosed arrhythmia within the previous 3 months,
• Hospitalisation within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) as per the New York Heart Association classification (www.americanheart.org),
• Thoracic surgery within the previous 24 months.
8. Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction. (However, patients with a diagnosis of these conditions but well-controlled, stable and without symptoms due to stable concomitant medication for its treatment are allowed to enter trial).
9. Presence of narrow-angle glaucoma.
10. History of untoward reactions or known hypersensitivity to inhaled anticholinergics (including aclidinium bromide), ß2 adrenergic agonists or inhaled medication or any component thereof (including report of paradoxical bronchospasm).
11. Life expectancy of less than 1 year.
12. QTc [calculated according to Bazett’s formulae (QTc=QT/RR1/2) above 470 milliseconds in the ECG performed at Screening Visit, as indicated in the centralised reading report.
13. Clinically relevant abnormalities in laboratory results, ECG parameters (other than QTcB), or physical examination if the abnormality defines a disease state listed as an exclusion criterion, except for those related to COPD.
14. Clinically significant diseases other than COPD, which, in the opinion of the investigator, may put the patient at risk because of the participation in the trial; or diseases which may influence the results of the study or the patient’s ability to take part in it.
15. Patient who does not maintain regular day/night, waking/sleeping cycles (e.g., history of sleep apnoea syndrome, any disease related with sleep disturbances such as restless-legs syndrome or somnambulism). Moreover, night shift workers will be excluded.
16. Patient who intends to use any concomitant medication not permitted by this protocol or who have not undergone the required washout period for a

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified